The hydroalcoholic extract of Salvia elegans induces anxiolytic- and antidepressant-like effects in rats.

Behavioral effects of a hydroalcoholic (60% ethanol) extract from the leaves of Salvia elegans Vahl (Lamiaceae) were studied in male Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Putative anxiolytic and antidepressant properties of Salvia elegans were studied in the elevated plus-maze test (EPM) and in the forced swimming test (FST), respectively. Deleterious effects of Salvia elegans on learning and memory were also studied by using active and passive avoidance paradigms. The results revealed that all doses (3.12, 12.5, 25 and 50 mg/kg) of the extract caused a significant decrease in total motility, locomotion, rearing and grooming behavior. Only the dose of 12.5 mg/kg increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg). In the FST, all doses of the extract induced a reduction of immobility, in a similar way to that of fluoxetine (10 mg/kg) and imipramine (12.5 mg/kg), along with a significant increase in the time spent in swimming behavior. Acquisition of active avoidance responses was disrupted by pre-treatment with the extract, but retention of a passive avoidance response was not significantly modified. These results suggest that some of the components of the hydroalcoholic extract of Salvia elegans have psychotropic properties, which deserve further investigation.

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: morphological and behavioural evidence.

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from Aloysia polystachya in rats.

Behavioral effects of a hydroalcoholic extract from leaves of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) were studied in female Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Anxiolytic-like properties were studied in the elevated plus-maze (EPM) test and the possible antidepressant-like actions were evaluated in the forced swimming test (FST). The results revealed that high doses of the extract (25 and 50 mg/kg, i.p.) caused a significant decrease in total motility, locomotion, rearing and grooming behavior. All doses injected (from 1.56 to 50 mg/kg) increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg, i.p.). In the FST, the extract (12.5, 25 and 50 mg/kg) was as effective as fluoxetine (10 mg/kg, i.p.) and imipramine (12.5 mg/kg, i.p.) in reducing immobility, along with a significant increase in swimming and climbing, respectively. These results suggest that some of the components of the hydroalcoholic extract of A. polystachya, such as thujone and carvone among others, may have sedative, anxiolytic and antidepressant-like properties which deserve further investigation.

Central nervous system activity of the hydroalcoholic extract of Casimiroa edulis in rats and mice.

In order to evaluate the effects produced by the hydroalcoholic extract of leaves from Casimiroa edulis on the central nervous system, different behavioral tests and animal models of depression and anxiety were performed. The extract was administered intraperitoneally in male and female rats and tested on spontaneous motor activity, locomotor activity, exploration of an elevated plus-maze (EPM) and in the forced swimming test (FST). In addition, the extract was administered orally in male and female mice and evaluated in the following tests: general observation, pentobarbital-induced hypnosis, EPM, rota-rod, hole-board, and marble-burying. The results revealed that, in rats, the extract caused considerable reduction of locomotor and exploratory activities and increased the exploration of the EPM open arms in a similar way that diazepam. In the FST, the extract was as effective as fluoxetine in inducing shortening of immobility, along with a significant increase on climbing duration. On the other hand, in mice, the extract prolonged pentobarbital-induced hypnosis, increased exploration of the EPM open arms and partially protected from the pentylenetetrazol-induced convulsions. No significant effect was evident on motor coordination, hole-board and marble-burying tests. These results suggest that the hydroalcoholic extract of Casimiroa edulis may contain sedative principles with potential anxiolytic and antidepressant properties, which need further investigation.

Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats.

The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased open-arm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.

Progesterone effects on the acquisition of conditioned avoidance responses an other motoric behaviors in intact and ovariectomized rats.

This study demonstrates a significant impairment in the acquisition of conditioned avoidance responses in female rats during their estrus phase. Progesterone (PROG 5 mg) injected 6 h prior to the test, significantly enhanced the performance exhibited by rats at estrus, but not at diestrus. In ovariectomized rats, the acquisition of conditioned avoidance responses was similar to the exhibited during diestrus and this behavior was depressed by a single dose of estradiol benzoate (EB 2 micrograms) injected 48 h prior to the test. PROG antagonized the avoidance depression induced by EB, but it was not able to induce changes in the acquisition of conditioned avoidance response in ovariectomized rats without EB pretreatment. Estradiol appears to be the principal ovarian steroid modulating the acquisition of an avoidance task, whereas PROG seems to have a secondary role in this behavior, regulating the actions of estradiol on the brain. PROG failed to induce consistent changes in some spontaneous motor behaviors in intact and ovariectomized rats.

Luteinizing-hormone-releasing hormone modifies retention of passive and active avoidance responses in rats.

The influence of posttraining subcutaneous administration of luteinizing-hormone-releasing hormone (LHRH) was tested on the retention of either active or passive avoidance conditioning in male rats. Injection of LHRH (200 micrograms/kg) immediately after the acquisition of an active avoidance response (two-way shuttle behavior) enhanced retention of the response, assessed 7 days later. When the neuropeptide was injected immediately after a passive avoidance conditioning training, the effects varied with the intensity of the footshock applied. LHRH enhanced retention of avoidance training with weak footshock (0.20 and 0.35 mA) but impaired retention of training with strong footshock (0.70 and 1.0 mA). The effects of LHRH seem to be unspecific since they are similar to those observed after treatment with several hormones. The results are discussed based on the interactions between peripherally injected hormones and endogenous substances released following footshock. A modulatory effect on the monoaminergic pathway involved in memory storage processes is postulated.

Effects of estradiol replacement in ovariectomized rats on conditioned avoidance responses and other behaviors.

The acquisition of conditioned avoidance responses along with spontaneous behaviors were studied in ovariectomized rats. Fourteen days after ovariectomy, they were injected subcutaneously with one of the following doses of estradiol benzoate: 0.2, 2 or 20 microgram/rat. Behavioral tests were applied 3, 24, 48 or 72 hours after estradiol treatment. Although estradiol 2 microgram/rat induced a decrease in acquisition of conditioned avoidance responses at all times tested, this effect was maximum at 48 h. Estradiol 0.2, and 20 microgram/kg decreased and stimulated, respectively, the acquisition performance, as tested 3 h after injection. All doses increased global motility and rearing behavior. This hypermotility disappeared at 24 h, but it was observed again at 48 and 72 h after estradiol 0.2 and 20 microgram/rat. The hormone also induced an increase in head shaking and a decrease in grooming. Although the behavioral changes are more significant in presence of very low serum levels of estradiol, they seem to be triggered by the previous increase in the estradiol levels. The possible sites and mechanisms of action of estradiol on behavior are discussed.

LHRH and rat avoidance behavior: influence of castration and testosterone.

Pretraining subcutaneous administration of a high dose of LHRH (100 micrograms/kg) to intact rats impaired acquisition of a conditioned avoidance response (CAR) in a two way shuttle box. Acquisition of a CAR was also decreased when LHRH was administered to castrated rats. LHRH antagonized the dose related impairment in acquisition and retention performance induced by testosterone in castrated animals. The results are discussed based on the interrelationships between castration, testosterone, LHRH and brain monoamines.

Influence of the estrous cycle, ovariectomy and estradiol replacement upon the acquisition of conditioned avoidance responses in rats.

The changes in the acquisition of conditioned avoidance responses (CARs) and the performance of some spontaneous behaviors were examined across the estrous cycle of female rats. CARs were facilitated during diestrus, impaired at proestrus and practically abolished at estrus and metestrus. Motor activity and head shaking were minimally affected with the stages of the cycle. Motor activity was increased at metestrus and head shaking decreased at estrus. At 14 days following ovariectomy, there was a significant enhancement of CARs which was antagonized by the daily administration of estradiol benzoate (10 micrograms/kg) for three days. Ovariectomy also increased grooming behavior and estradiol replacement returned grooming to its basal level. The results suggest an inhibitory control of estradiol on CARs and grooming. The involvement of other hormones which also varied across the estrous cycle and its interaction with brain catecholamine systems, particularly dopamine, are discussed.

Inhibition of DT-diaphorase potentiates the in vivo neurotoxic effect of intranigral injection of salsolinol in rats.

The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 microl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when they were stimulated with apomorphine (0.5 mg/kg, s.c.), similar to rats injected unilaterally with 6-hydroxydopamine (6-OHDA). These rats also exhibited impairment of motor and cognitive behaviours. The results support the hypothesis that DT-diaphorase plays a protective role in the nigrostriatal dopaminergic systems.

Effects of pretreatment with luteinizing hormone releasing hormone (LHRH) on behaviors induced by apomorphine in rats.

The influence of LHRH on the behavioral effects induced by apomorphine (APO) was studied in male rats. Several doses of apomorphine (31.25, 62.5, 125, 250 and 500 micrograms/kg) were administered subcutaneously (SC) after LHRH 100 micrograms/kg or solvent. Low doses of apomorphine induced hypomotility and impaired acquisition of a conditioned avoidance response (CAR). High doses produced hypermotility, stereotyped sniffing and a short lasting increase, followed by a decrease in the acquisition of CARs. Pretreatment with LHRH potentiated the hypomotility induced by low doses of apomorphine (62.5 and 125 micrograms/kg) and the hypermotility, stereotyped sniffing and the enhancement in acquisition of CARs produced by higher doses of apomorphine (250 and 500 micrograms/kg). These findings suggest that LHRH could indirectly regulate dopamine activity through an increase in sensitivity of dopamine receptors (pre- and postsynaptic), which mediate the behavioral effects of APO. It is postulated that this hypersensitivity of DA receptors could be the consequence of an inhibition of presynaptic dopaminergic transmission, induced by LHRH.

LHRH antagonizes yawning and genital grooming induced by apomorphine in rats.

The effects of the pretreatment with LHRH on the behavioral effects induced by low doses of apomorphine were studied in male rats. Three doses of apomorphine (31.25, 62.50 and 125 micrograms/kg) were subcutaneously administered two hours after LHRH 100 micrograms/kg or solvent SC treatment. Apomorphine induced repeated episodes of yawning and genital grooming. Pretreatment with LHRH abolished or reduced yawning and genital grooming induced by the three doses of apomorphine, suggesting that the peptide could induce subsensitivity of DA receptors responsible for yawning and genital grooming.

Pharmacological evidence of catecholaminergic involvement in the behavioral effects of luteinizing hormone releasing hormone in rats.

The influence of L-DOPA on the behavioral effects of LHRH was studied in male rats. Subcutaneous administration of LHRH (100 micrograms/kg) caused a significant disruption in the acquisition of a conditioned avoidance response (CAR) and a significant increase in head shaking behavior (HSB). Pretreatment with this hormone antagonized the stimulatory action of amphetamine (1 mg/kg, IP) in acquisition of CARs, spontaneous motor activity (SMA) and rearing behavior (RB). L-DOPA (100 mg/kg, IP), administered after LHRH, stimulated SMA, RB and HSB. In addition L-DOPA antagonized the effect of LHRH on acquisition of CARs and counteracted the antagonism between LHRH and amphetamine in acquisition of CARs and SMA. These findings indicate that LHRH could exert its behavioral effects through an inhibitory action upon brain catecholamine synthesis. The suppression of CARs may be the response to DA antagonism and the interaction with amphetamine could be mediated by an inhibition of both DA and NE activities. The possibility of an interaction between LHRH and central serotonin mechanisms is also discussed.

Influence of luteinizing hormone releasing hormone (LHRH) on the behavioral effects of amphetamine in rats.

The influence of luteinizing hormone releasing hormone (LHRH) on the behavioral effects induced by several doses of D-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg IP) was studied. A dose response relation was previously established for the effects of LHRH (50, 100 and 200 micrograms/kg SC) on acquisition and retention of conditioned avoidance responses (CARs). The neuropeptide impaired acquisition and improved retention of CARs, without modifying spontaneous motor activity. Pretreatment with 100 micrograms/kg of LHRH antagonizes the enhancement in acquisition of CARs due to D-amphetamine 0.5, 1.0 and 2.0 mg/kg, the impairment in retention induced by amphetamine 1.0 and 2.0 mg/kg, and the hypermotility and the increased rearing behavior induced by amphetamine 1.0 and 2.0 mg/kg. These results suggest that brain catecholamines, particularly dopamine, could play a role in the behavioral effects of LHRH. Interactions between LHRH and central dopaminergic mechanisms are discussed.

Effect of oxotremorine on the acquisition of a conditioned avoidance response is modified by the estrous cycle, ovariectomy, and estradiol replacement in rats.

This study was designed to evaluate the influence of the hormonal status of the rat on the effects of a potent reversible muscarinic agonist, oxotremorine, on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous motor behaviors. Oxotremorine (OXO 50 and 100 micrograms/kg, intraperitoneally) given 5 min before testing improved active conditioned avoidance in intact female rats at estrus and in ovariectomized rats after estradiol replacement, and impaired performance in female rats at diestrus and after ovariectomy without estradiol replacement. No significant differences due to hormonal status of the rat in some spontaneous motor behaviors were observed. In fact, OXO in this dose range failed to induce significant changes in spontaneous motor activity, the number of rears diminished, and the time spent in grooming behavior increased in all groups studied. These results provided behavioral evidence for the hypothesis that central cholinergic activity is function of the hormonal status of the animal. Relationships between ovarian hormones and cholinergic system are discussed.

Ketanserin effects on rat behavioral responses: modifications by the estrous cycle, ovariectomy and estradiol replacement.

The present investigation was designed to explore the influence of estrous cycle phase, ovariectomy, and estradiol replacement on the behavioral effects of the 5-HT2 receptor antagonist, ketanserin. The parameters under investigation were ketanserin-influenced acquisition of conditioning avoidance responses (CARs), and the performance of some spontaneous motor behaviors. Ketanserin (KET 3 mg/kg) injected subcutaneously 30 min before testing improved active conditioned avoidance in intact female rats at estrus, and in ovariectomized (OVX) rats with estradiol replacement. Furthermore, KET impaired performance in female rats at diestrus and after ovariectomy. In male rats, which were included in this study in order to compare their behavioral responses with those exhibited by female rats, KET administration enhanced acquisition of CARs. These results provide behavioral evidence for the hypothesis that central serotonergic activity is a function of the hormonal status of the animal. An additional segment of the present study focussed on motoric behaviors. Spontaneous motor activity, number of rears, and time spent in grooming behavior were significantly increased by KET in all groups studied. In contrast, blockade of 5-HT2 receptors failed to induce significant changes in the number of head shakes. Relationships between ovarian hormones and the central serotonergic system are discussed.

Effects of LHRH on avoidance conditioning in normally cycling and ovariectomized female rats.

Several studies have demonstrated that the peptide LHRH can modify behavior in the male rat. Peripheral and intracerebral infusions of LHRH impair the acquisition of conditioned avoidance responses (CARs) and increase some spontaneous motor behaviors, such as head shaking and grooming. The present study was undertaken to detect the effects of LHRH on the acquisition of CARs and spontaneous motility in normally cycling and ovariectomized (OVX) Sprague-Dawley female rats. Normally cycling females were separated in four groups, according to the stage of the estrous cycle. Ovariectomized female rats were pretreated, 48 h before the experiment, with estradiol benzoate (10 microg/kg) or corn oil. LHRH (6.25, 25, or 50 microg/kg) was subcutaneously injected and the behavioral tests began 1 h after. Low doses of LHRH stimulated the acquisition of CARs during proestrus, estrus, and metestrus, whereas higher doses impaired conditioning in all the four stages of the cycle. High doses of LHRH impaired acquisition in OVX rats treated with oil and potentiated the depressant effects of EB on this behavior. The effects of LHRH on spontaneous motor activity were either stimulatory or inhibitory, according to the hormonal status and the dose administered. High doses of LHRH decreased motor responses in the diestrous rat. All the doses of LHRH increased the number of headshakes during proestrus, estrus, and metestrus, while the other motor responses were scarcely or not affected by LHRH in these stages. In OVX rats LHRH increased rearing, head shaking, and grooming behavior. These results support a role of LHRH in the modulation of conditioned and spontaneous behavior. They could provide an explanation to the behavioral changes observed across the estrous cycle and those observed after EB priming in OVX rats.

Behavioral effects of intracerebral administration of luteinizing hormone releasing hormone (LHRH) in rats.

The effects of LHRH intracerebrally infused on acquisition of conditioned avoidance responses (CARs) and spontaneous motility were studied in adult male rats. The results were the following: 1) LHRH (1 and 2.5 micrograms/rat) administered through a cannula stereotaxically implanted into the lateral ventricle induced an impairment in the acquisition of CARs along with an increase in global motility, rearing, head shaking and grooming behavior; 2) LHRH 1 microgram/rat injected into the hippocampus or nucleus accumbens induced also an impairment in acquisition which is evident 15 min after treatment. In contrast, intrastriatal injection induced an immediate disruption of this behavior; and 3) there is a good dose-response relationship for intrastriatal LHRH between 7.8 and 62.5 ng/rat. The results suggest that the estriatum could be the locus of the LHRH-induced inhibition of CARs. Then the possibility of an involvement of the dopamine nigrostriatal system is discussed.

Influence of the estrous cycle and estradiol on the behavioral effects of amphetamine and apomorphine in rats.

This experiment was designed to investigate the influence of hormonal status of the rat on the effects of two doses of an indirect-acting dopamine agonist (amphetamine 0.25 and 1.0 mg/kg, IP) and a direct-acting dopamine agonist (apomorphine 62.5 and 250 micrograms/kg, SC) on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous behaviors. Active conditioned avoidance was improved by amphetamine in all the groups except in females at diestrus; apomorphine improved this response only in females at estrus and in ovariectomized rats after estradiol replacement, but the avoidance response was deteriorated in males and females at diestrus and after ovariectomy without estradiol replacement. Both dopaminergic drugs had contrasting effects on motor activity, number of rearings, and number of head shakes according to the hormonal status of the rat. Only the time spent in grooming behavior decreased after the treatment with both dopamine agonists in all of the five groups studied. These results provided behavioral evidence for the hypothesis that dopaminergic activity in the CNS is affected distinctively by modifications in the sexual hormone status (gender, estrous cycle, ovariectomy, and estradiol replacement). Relationships between ovarian hormones and dopaminergic system are discussed.